1. Technical Field
The present invention relates to a crosslinkable pressure-sensitive adhesive for skin, to a crosslinkable pressure-sensitive adhesive sheet for skin employing it, to a composition for production of the crosslinkable pressure-sensitive adhesive for skin and to a process for production of the crosslinkable pressure-sensitive adhesive for skin.
2. Background Art
Pressure-sensitive adhesive sheets for skin, in general, must reliably adhere for about 24 hours after being attached to skin and must also adhere without peeling during perspiration and bathing. Also for removal, they must be peelable with a degree of force that does not cause pain, and if the adhesion is stronger than necessary it can result in plucking of hairs and peeling of the corneum, as well as mechanical skin irritation by pulling of the skin. Consequently, this creates erythema that may persist for several days even after peeling, and therefore it is necessary to minimize this inconvenience. Moreover, it is important that no pressure-sensitive adhesive remain on the skin surface after the pressure-sensitive adhesive sheet has been removed from the skin.
Crosslinking of acrylic pressure-sensitive adhesives has been commonly employed in the prior art in pressure-sensitive adhesives for skin in order to improve cohesion of the pressure-sensitive adhesives. Such crosslinking is achieved almost entirely by using the acrylic acid in an acrylic copolymer, but its drawbacks include the facts that (1) the adhesion is excessively strong or chemical activity of the acrylic acid causes significant skin irritation, (2) in percutaneous absorption preparations containing drugs, the acrylic acid and basic drug interact and impede migration of the drug from the pressure-sensitive adhesive into the skin, thereby reducing the percutaneous absorption, and (3) polyisocyanate used as the crosslinking agent is highly active and often reacts with drugs, thereby impairing drug stability.
In Japanese Patent Laid-open (Kokai) Publication SHO No. 61-100520 there is proposed an acrylic acid-free pre-crosslinked pressure-sensitive adhesive, which comprises 45 mol % 2-ethylhexyl acrylate, 20-55 mol % vinylpyrrolidone and no greater than 35 mol % of an acrylic acid ester with 3-12 carbon atoms in the ester portion, as well as 0.005-0.5 wt % of a polyfunctional monomer with respect to the weight of the entire monomer. However, while percutaneous absorption preparations using this type of pressure-sensitive adhesive have satisfactory drug percutaneous absorption and stability, the cohesive strength is insufficient when softening agents and plasticizers are added to improve the drug release property, and therefore adhesive residue remains on the skin after the percutaneous absorption preparation is removed. Thus, the problem of adhesive residue must be solved in order to obtain excellent pressure-sensitive adhesive sheets for skin.
As modifications to crosslinking acrylic-based pressure-sensitive adhesives there have been proposed methods of obtaining pressure-sensitive adhesive sheets by crosslinking after coating and drying acrylic copolymer composition solutions containing large amounts of plasticizers, and specifically there may be mentioned Japanese Patent Publication No. 2700835 and Japanese Patent Publication No. 3014188. With such percutaneous absorption preparations, however, it is possible to increase the shape retention of the pressure-sensitive adhesive layer but difficult to design a preparation with balance between adhesion on the skin and cohesive force of the pressure-sensitive adhesive.
On the other hand, Japanese Patent Laid-open (Kohyo) Publication No. 2002-535475 proposes a method wherein an acrylic-based pressure-sensitive adhesive containing diacetoneacrylamide, and a plasticizer, are mixed with a polyamine such as adipic acid dihydrazide or hexanediamine, the mixture is coated and then the solvent is heated and dried for crosslinking.
However, the drawbacks of this method are the following: (1) Mixture of the low-molecular polyamine such as adipic acid dihydrazide or hexanediamine with the pressure-sensitive adhesive solution results in a coating mixture that gels within several hours and becomes impossible to coat.(2) Low molecular polyamines such as adipic acid dihydrazide and hexanediamine crosslink the diacetoneacrylamide-containing acrylic-based pressure-sensitive adhesive when no drug is present, but in the presence of a drug they react therewith or the drug often interferes, thereby preventing crosslinking.(3) Adipic acid dihydrazide has low organic solvent solubility, and therefore must be used as a solution in water for addition to the coating solution. Consequently, its use in a large amount promotes precipitation of polymers and renders handling inconvenient.(4) Hydrazine compounds such as adipic acid dihydrazide are absorbed through the skin and are indicated as a toxicity risk, for which reason they have been unsuitable as additives for pressure-sensitive adhesives on skin.